Preclinical evaluation of a chimeric malaria vaccine candidate in Montanide ISA 720®

Several malarial antigens are in development as potential vaccine candidates as part of a concerted effort to control the disease, which kills more than one million people per year. Although some antigens have demonstrated an impact against the malaria parasite, Plasmodium falciparum, many researchers hypothesize that a combination of antigens will be required to generate high levels of efficacy against clinical disease. PfCP2.9 is a chimeric protein that includes MSP1(19) and domain III of AMA1 [AMA1 (III)] of Plasmodium falciparum in a single recombinant molecule. The antigen, formulated in Seppic's ISA 720 adjuvant, is approaching Phase I clinical testing in humans. The purpose of this study was to assess the safety of this vaccine and to explore possible dosage levels for clinical evaluation. Groups of five monkeys each were immunized i.m. with 25 mu g, 50 mu g, 100 mu g and 200 mu g of PfCP2.9/ISA 720 in 0.5 mL on days 0 and 112. The mean anti-PfCP2.9 titres to the 50 mu g dose group were higher than the other dose groups; however, there was no statistically significant difference between the anti-CP2.9 titres of any of the groups, suggesting that the immune response to PfCP2.9 was saturated at 25 mu g. One animal in the 100 mu g dose group elicited a higher antibody and IFN-gamma response to PfCP2.9 than the rest of the cohort; this animal developed a small sterile abscess following the second vaccination, which spontaneously resolved within one week. In conclusion: (a) 50 mu g is highly immunogenic, appears safe, and is likely to be an appropriate dose for clinical evaluation; and (b) a conservative trial design is warranted to avoid any unexpected reactogenicity with the PfCP2.9/ISA 720 formulation.